Abstract 1414: Assessment of the Cancer Testis antigen AKAP4, via tumor expression analysis and IHC, as a potential vaccine and immunotherapy target for colorectal cancer

Abstract

Abstract Introduction: Cancer-Testis antigens (CTA’s) are normally expressed in germline tissue, however, aberrant expression occurs in some cancers. Restricted CTA expression in normal tissues make CTA’s potential vaccine targets. CTA’s have been associated with tumor cell proliferation and invasion. The CTA A-kinase anchor proteins 4 (AKAP 4) plays a role in cancer development and progression. The expression pattern of AKAP4 gene in CRC is not well characterized. This study’s aim was to assess AKAP4 expression in CRC and to assess this CTA’s potential as a vaccine target. Methods: CRC patients (pts) undergoing surgery who donated tissue to an IRB approved tissue/data bank comprise the study group. Demographic and pathologic data were assessed. Tissues were OCT embedded and stored at -800C. Total purified RNA was isolated from tissue samples and cDNA synthesized. AKAP4 expression was analyzed by quantitative PCR (QPCR) using EXPRESS qPCR universal Supermix and Taqman assay. Comparative quantitative analysis was performed based on the delta-delta Ct method with GAPDH as internal control. Tumor and testis AKAP4 expression levels were determined; tumors with levels 0.1% or more than the testis was considered positive. Immunohistochemistry (IHC) was performed on a subset of tumor and normal tissue. The impact of tumor location and cancer stage on AKAP4 expression was determined and assessed (Wilcoxon signed rank test). Results: 70 paired CRC and normal tissue specimens (35 M/36 F, age 67.8±14) were studied (86% colon,14% rectal; cancer stage: 1, 24%; 2,37%; 3, 31.%;stg 4, 7%). The percent of pts with a relative Malignant to Normal tissue AKAP4 expression ratio (MN) over 1 was 17%; the percent with both MN ratio over 1 and expression levels above 0.1% of testis levels was 16%. IHC demonstrated AKAP4 in a subset of CRC tumor samples. No significant difference was noted between colon vs rectal, or cancer stage groups. No expression was found in 21 normal samples. Discussion: In a tumor subset the relative expression of AKAP4 was above that of normal colon and more than 0.1% of testis expression. IHC study demonstrated the antigen in CRC tumors. A larger study is needed determine if AKAP4 expression correlates with T, N, or final tumor stage. AKAP4 holds some promise as a vaccine target. Citation Format: Chandana S. K. Herath Mudiyanselage, Neil Mitra, Otavia L. Caballero, Dasuni N. Gamage, Xiaohong Yan, Vesna Cekic, Joseph Martz, Richard L. Whelan. Assessment of the Cancer Testis antigen AKAP4, via tumor expression analysis and IHC, as a potential vaccine and immunotherapy target for colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1414.